DESCRIPTION (Adapted from applicant's abstract and specific aims): Aging is associated with many pathophysiological changes which affect most organ systems of the body, including the lungs. A large volume of work has been published examining the alterations in systemic vascular control mechanisms associated with the aging process. In contrast, relatively little work has attempted to elucidate the derangements in pulmonary vascular control in aged animals. The application hypothesizes that aging is associated with diminished pulmonary vascular reactivity, manifested as reductions in both pressor and depressor responsiveness. The specific aims are: 1) determine the scope of altered pulmonary vascular responsiveness in normal aging; 2) determine the scope of altered pulmonary vascular responsiveness in aged diabetic rats; 3) examine alterations in pulmonary vascular smooth muscle cellular second messengers in aging and diabetes; and 4) examine alterations in pulmonary vascular smooth muscle and endothelial cell calcium handling in aging and diabetes.